Short answer: Both copy alpha-MSH, the hormone that darkens skin. Melanotan 1 is afamelanotide, FDA approved as Scenesse, a 16 mg implant every 2 months for the light-sensitivity disorder EPP.1 Melanotan II is a smaller ring-shaped peptide that has never been approved; its early studies also found erections and nausea.2 FDA notes case reports of melanoma and other serious events with Melanotan II.3
| Melanotan 1 (afamelanotide) | Melanotan II | |
|---|---|---|
| Structure | Linear 13-amino-acid alpha-MSH analog1 | Ring-shaped (cyclic) 7-amino-acid analog of part of alpha-MSH2 |
| Main receptor | Binds mainly to MC1R, the skin pigment receptor1 | Not stated in the abstracts cited here; early studies found tanning plus erections, yawning and nausea2 |
| FDA status | Approved as Scenesse (initial approval 2019)1 | Never approved. Nominated for compounding, then withdrawn; FDA lists safety concerns3 |
| Approved use | Adults with a history of phototoxic reactions from erythropoietic protoporphyria (EPP)1 | None |
| Label or study dosing | One 16 mg implant under the skin every 2 months, placed by a trained clinician1 | 0.01 to 0.03 mg/kg under the skin in a 3-man pilot study; 0.025 mg/kg in erectile dysfunction studies24 |
| Half-life | About 15 hours from the slow-release implant; median time to peak 36 hours1 | No published human figure in the sources we checked |
| Common side effects | Implant site reaction 21% vs 10% on placebo; nausea 19% vs 14%1 | Nausea, stretching and yawning, spontaneous erections25 |
| Skin warnings | Darkening of existing moles and freckles; full-body skin check twice a year1 | FDA cites case reports of melanoma, among other serious events3 |
Scenesse is a 16 mg afamelanotide rod placed under the skin above the hip every 2 months. In one trial of 93 people with EPP, the median time spent in direct sunlight without pain over 180 days was 64.1 hours on Scenesse vs 40.5 hours on placebo. In a second trial of 74 people, it was 6.0 vs 0.75 hours over 270 days, measured differently.1
Patients still need sun protection. The label warns about serious allergic reactions and darkening of moles and freckles, and recommends a full-body skin check twice a year.1
In a 1996 pilot study, 3 men got Melanotan II under the skin on alternating days for 2 weeks. Two showed darker skin on the face, upper body and buttocks a week after dosing ended. Mild nausea was common, one man had marked sleepiness and fatigue at the top dose, and spontaneous erections lasted 1 to 5 hours after dosing.2
Two small trials then tested it for erectile dysfunction. Erections appeared in 8 of 10 men with psychogenic ED, and in 12 of 19 injections vs 1 of 21 placebo doses in men with physical risk factors, where 4 of 19 injections caused severe nausea.45 That line of work led to bremelanotide; see PT-141 vs Melanotan II: how do they differ?.
Unlicensed Melanotan powders are not the approved implant. Early human work on Melanotan 1 used injections under the skin, which were fully absorbed, while the same compound taken by mouth gave no measurable blood levels.6 For Melanotan II, FDA notes risk of immune reactions and published case reports of melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism.3 These are study protocols, not personalized advice; confirm any dosing with your prescriber.
More detail: the Melanotan 1 (Afamelanotide) and Melanotan II guides.